Imai Naohiko, Kaur Tarundeep, Rosenberg Mark E, Gupta Sandeep
Division of Renal Diseases and Hypertension, Stem Cell Institute and Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Semin Dial. 2009 Nov-Dec;22(6):629-35. doi: 10.1111/j.1525-139X.2009.00654.x.
The understanding of cellular sources of kidney regeneration has rapidly evolved in the last decade. It is now believed that regeneration occurs predominantly from cells that reside within the injured kidney, with minimal contribution from extra-renal cells. We now know that improved kidney regeneration seen following exogenous administration of stem cells occur predominantly by noncellular paracrine mechanisms. Of all extra-renal stem cells, mesenchymal stem cells (MSC) are the most promising stem cell type for treating kidney diseases. There is an ongoing clinical trial evaluating safety and efficacy of MSC in treating acute kidney injury (AKI). Results of this trial are expected to bring use of MSC closer to the clinical realm. An improved understanding of the small molecules that facilitate kidney regeneration and are secreted by MSC will likely result in the development of new therapies for treating AKI. Identification of adult stem cell markers will result in improved understanding of pathophysiology of kidney diseases and could lead to the development of new cellular therapies. Directed differentiation of stem cells into desired cell types such as erythropoietin producing cells will allow selective replacement of lost kidney function. Cell-based therapies for patients with chronic kidney disease are presently in proof-of-principle stage and are expected to evolve in the coming years with improved understanding of stem cell biology. Technological advancement in cellular therapy is expected to provide improved therapeutic options for patients with kidney diseases in the near future.
在过去十年中，对肾脏再生细胞来源的认识迅速发展。现在人们认为，再生主要发生于受损肾脏内的细胞，肾外细胞的贡献极小。我们现在知道，外源性给予干细胞后肾脏再生的改善主要通过非细胞旁分泌机制实现。在所有肾外干细胞中，间充质干细胞（MSC）是治疗肾脏疾病最有前景的干细胞类型。目前正在进行一项评估MSC治疗急性肾损伤（AKI）安全性和有效性的临床试验。该试验结果有望使MSC的应用更接近临床领域。更好地了解由MSC分泌的促进肾脏再生的小分子，可能会带来治疗AKI的新疗法。鉴定成体干细胞标志物将有助于更好地理解肾脏疾病的病理生理学，并可能导致新细胞疗法的开发。将干细胞定向分化为所需的细胞类型，如促红细胞生成素产生细胞，将能够选择性地替代丧失的肾功能。针对慢性肾病患者的细胞疗法目前正处于原理验证阶段，预计未来几年随着对干细胞生物学理解的加深会不断发展。细胞治疗技术的进步有望在不久的将来为肾病患者提供更多更好的治疗选择。
